This application proposes a three-year renewal of a KOI International Research Scientist Career Development Award focused on characterizing T-cell immune responses to Vibrio cholerae infection. The program will be conducted under the collaborative mentorship of Drs. Stephen B. Calderwood and Edward T. Ryan, Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts and Dr. Firdausi Qadri, Laboratory Sciences Division, International Centre for Diarrhoeal Diseases Research, Dhaka, Bangladesh. The candidate is trained in Pediatric Infectious Diseases and has a documented commitment to an independent clinical research in the field of international pediatric infectious diseases. The research component ofthe proposal includes three specific aims: (1) To compare the characteristics of CD4+ T-cell responses to V. cholerae antigens in cholera patients and vaccines;(2) To evaluate mucosal CD4+ T-cell responses in cholera patients;and (3) To evaluate the association between initial CD4+ T-cell responses and the development and maintenance of B cell memory to V. cholerae. The mentors and supporting faculty will assist with the progress of the applicant's research and career development. The program will allow the candidate to develop as an independent biomedical researcher in international pediatric infectious diseases, and data generated under the proposed program will enable the candidate to apply for independent NIH funding for future studies of immunologic responses to cholera and other enteric infections. PUBLIC HEALTH RELEVANCE: Vibrio cholerae is estimated to cause 3 to 5 million cases of secretary diarrhea and over 100,000 deaths annually. Although symptomatic infection with V. cholerae results in durable immunity, vaccines have failed to induce comparable protection against disease. An improved understanding of T-cell responses to natural cholera and vaccination may lead directly to improvements in cholera vaccines.